Endoscopic ultrasound as a reliable tool for assessment of pancreatic adenocarcinoma treatment: Example of in situ gene therapy

Abstract

Background and study aims In pancreatic cancer, the antitumor effect can only be assessed by means of a computed tomography (CT) scan using RECIST (Response Evaluation Criteria in Solid Tumours) criteria. The aim of this study was to assess the intra-observer and interobserver agreement of endoscopic ultrasound (EUS) imaging in assessing tumor volume in primary pancreatic cancer. Patients and methods During a Phase 1 gene therapy trial, 21 patients had EUS before the first and second EUS-guided in situ gene therapy injections. All anonymized EUS files were then randomly distributed to three gastroenterologists/endosonographers and three radiologists (blind status). The largest tumor diameter was measured and the intraclass correlation coefficient (ICC) was determined. Results Intra-observer and interobserver agreements were good to excellent, regardless of operator experience (junior versus senior member of staff) (ICC: 0.65 to 0.84). A comparison of pretreatment and post-treatment measurements by the investigators highlighted a significant antitumor effect (-11 %; P = 0.0098), similar to that obtained during the generic protocol (-10 %; P = 0.0045). Conclusions Interobserver agreement regarding primary pancreatic adenocarcinoma measurements appears good to excellent, thus paving the way for the future inclusion of EUS assessments, particularly in trials assessing local therapies for pancreatic tumors.

Fig. 1

Flowchart of the Thergap-1 trial. Vertical blue arrows indicate the times of EUS recordings immediately before administration of the CYL-02 (gene therapy product) intratumoral injection (V1 and V7); Each EUS-guided intratumoral injection of CYL-02 was followed by Gemcitabine infusions (1000 mg/m ² each week for 3 weeks per month – indicated by vertical grey arrows). CT, computed tomography.

Fig. 2

Method used to record the maximum volume of primary pancreatic adenocarcinoma on EUS images captured from the video recordings. On the printed sheet showing the selected image, a ruler was used to measure the maximum volume as drawn by the expert (M1 in cm). This value was divided by the ruler measurement between two bars of the centimeter scale shown vertically to the right of each picture.

Fig. 3

Assessment of the antitumor effect 1 month after in situ gene therapy plus gemcitabine infusions. Primary pancreatic adenocarcinoma volumes were measured before CYL-02 intra-tumoral injection at baseline (D1,V1) and after 1 month (D28, V7). The volume (maximum tumor size) at 1 month was compared to the baseline reading. a Measurements recorded in 17 patients by the principal investigator of the Thergap-1 trial (LB). b Measurements recorded in the same 17 patients by the six investigators in this study (AC, BB, BN, FM, OM, BM). Mean ± SD; the median value is shown in italics. *** P  = 0.0045. ** P  = 0.0098 (the paired Wilcoxon test).